Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics in order to find out exactly what each new gene or combination of new genes is up to... give us the rest of the story!

This case is probably just a good example of a trend that will continue to establish itself as evolution becomes a real science. Our genes and the processes that select for different combinations of them are likely to turn out to play more of a role in our behavior than people want to believe.

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

The bear variations can be housed in zoos around the world, with scientists popping in from time to time to study them (take blood samples, etc.).

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

The bear variations can be housed in zoos around the world, with scientists popping in from time to time to study them (take blood samples, etc.).

It's not that easy. Making knock-out mice takes several generations, and even then something can go wrong and you have to start over.

"Researchers involved with the Framingham Heart Study found that in men and women 50 and older, “total cholesterol per se is not a risk factor for coronary heart disease at all.”

Indeed, what the Framingham researchers meant in 1977 when they described LDL cholesterol as a “marginal risk factor” is that a large proportion of people who suffer heart attacks have relatively low LDL cholesterol."

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

The bear variations can be housed in zoos around the world, with scientists popping in from time to time to study them (take blood samples, etc.).

It's not that easy. Making knock-out mice takes several generations, and even then something can go wrong and you have to start over.

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

The bear variations can be housed in zoos around the world, with scientists popping in from time to time to study them (take blood samples, etc.).

They'll first have to create polar bears with a generation time of 10 weeks, like mice. These will be very tiny polar bears.

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

You're thinking small. Fix your gaze past the horizon. In a future where obesity is rampant, we need these genes to survive our future blubber-rich diet.

The law won't allow building our custom human. Reforms will take time. But we can start introducing these genes in pigs, to preserve them in case the polar bears go extinct. Then we will be able to create the ultimate fat man. Mankind will flourish once again!

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

The bear variations can be housed in zoos around the world, with scientists popping in from time to time to study them (take blood samples, etc.).

It's not that easy. Making knock-out mice takes several generations, and even then something can go wrong and you have to start over.

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

It will probably be a lot easier to just identify the genes, look for related genes in smaller model organisms (like mice), and then do knockout* studies with those.

Scientists, it's time to create new polar bear variations using every combination of possible "knock-out" (deleted) genes within the newly evolved heart genes group and closely study their characteristics

Working with polar bears in the lab would be a bit difficult, not to mention the politics involved.

The bear variations can be housed in zoos around the world, with scientists popping in from time to time to study them (take blood samples, etc.).

It's not that easy. Making knock-out mice takes several generations, and even then something can go wrong and you have to start over.

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

It will probably be a lot easier to just identify the genes, look for related genes in smaller model organisms (like mice), and then do knockout* studies with those.

Edit: or gene replacement

These are newly evolved genes specific to polar bears, which is clearly explained in the article. There are no related genes in smaller model organisms. Dropping polar bear genes into mice runs a very high risk of distorted results. These genes need to be studied in polar bears, not in foreign organisms.

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

It will probably be a lot easier to just identify the genes, look for related genes in smaller model organisms (like mice), and then do knockout* studies with those.

Edit: or gene replacement

These are newly evolved genes specific to polar bears, which is clearly explained in the article. Ther are no related genes in smaller model organisms. Dropping polar bear genes into mice runs a very high risk of distorted results. These genes need to be studied in polar bears, not in foreign organisms.

They're not new genes specific to polar bears. Rather, they're changes to existing genes shared with a variety of organisms. It would probably be easier to make transgenic mice strains with the same modified genes and get some sense of them that way.

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

It will probably be a lot easier to just identify the genes, look for related genes in smaller model organisms (like mice), and then do knockout* studies with those.

Edit: or gene replacement

These are newly evolved genes specific to polar bears, which is clearly explained in the article. Ther are no related genes in smaller model organisms. Dropping polar bear genes into mice runs a very high risk of distorted results. These genes need to be studied in polar bears, not in foreign organisms.

They're not new genes specific to polar bears. Rather, they're changes to existing genes shared with a variety of organisms. It would probably be easier to make transgenic mice strains with the same modified genes and get some sense of them that way.

This depends right? It depends on if these genese are in the common sections of proteins or in some part that's bear specific.

I wonder whether these gene discoveries can help us make our own human hearts more resistant to the damaging effects of cholesterol, through novel medicines.

Understanding what these polar bear genes are actually doing (coding for the creation of certain proteins, etc.) is the first step toward creating these novel medicines, hence the need for knock-out polar bear studies...

It will probably be a lot easier to just identify the genes, look for related genes in smaller model organisms (like mice), and then do knockout* studies with those.

Edit: or gene replacement

These are newly evolved genes specific to polar bears, which is clearly explained in the article. Ther are no related genes in smaller model organisms. Dropping polar bear genes into mice runs a very high risk of distorted results. These genes need to be studied in polar bears, not in foreign organisms.

They're not new genes specific to polar bears. Rather, they're changes to existing genes shared with a variety of organisms. It would probably be easier to make transgenic mice strains with the same modified genes and get some sense of them that way.

This depends right? It depends on if these genese are in the common sections of proteins or in some part that's bear specific.

They're bear specific, which is clearly explained in the article...

when they looked for genes that have changed rapidly, they came up with so many other things. One of the most obvious is a gene involved in cholesterol metabolism. Despite all the time since their split from a common ancestor, panda bears and brown bears have no differences in this gene. In contrast, polar bears have picked up nine different changes in this gene in the 400,000 years or so that they've been breeding separately.

when they looked for genes that have changed rapidly, they came up with so many other things. One of the most obvious is a gene involved in cholesterol metabolism. Despite all the time since their split from a common ancestor, panda bears and brown bears have no differences in this gene. In contrast, polar bears have picked up nine different changes in this gene in the 400,000 years or so that they've been breeding separately.

Except that's not what that says. All that is saying is that the genes have changed more rapidly in polar bears than in other bears. Other bears have those same genes and so do non-bear animals. These are not magic, bear-specific genes, only polar bear-specific forms of common genes. These are not novel genes.

From the article: "Mutations in all nine genes, including APOB, are associated with either atherosclerosis or cardiomyopathy in humans and other mammalian model organisms."

Other mammals have these same genes; they just don't have the exact same form of them. Take one of the modified forms, put it into well-known mouse background strain, and see how that transgenic strain develops differently from a cohort of the non-transgenic background strain.

Potentially. But how about we start seeing if there are some easy biochemical and cellular studies that can give us the answer first? :-)

These biochemical and cellular studies should be done concurrently, NOT "first".

Considering the generation time of a polar bear is 11 years, those biochemical and cellular studies would be done, and probably the genes put into mice too for good measure, before you could even begin to have a colony of enough mutant bears worth studying.

Also: Knockouts are only a first step. Some knockouts cause embryonic lethality or other problems. Since these are just mutated forms of genes all mammals have, we can study how those changes affect things. We don't need to do them in polar bears.

Potentially. But how about we start seeing if there are some easy biochemical and cellular studies that can give us the answer first? :-)

These biochemical and cellular studies should be done concurrently, NOT "first".

Considering the generation time of a polar bear is 11 years, those biochemical and cellular studies would be done, and probably the genes put into mice too for good measure, before you could even begin to have a colony of enough mutant bears worth studying.

Also: Knockouts are only a first step. Some knockouts cause embryonic lethality or other problems. Since these are just mutated forms of genes all mammals have, we can study how those changes affect things. We don't need to do them in polar bears.

Yes, some knockouts or combinations of knockouts cause embryonic lethality or other problems. That's a result worth noting. Other knockouts or combinations of knockouts will have other effects, also results worth noting. Getting all of these results is the goal of doing the research in the first place.

Genes often aren't context-free. They often interact with other genes located far away. When a polar bear gene interacts with the rest of the polar bear genome - or, via the knockout process, fails to interact with the rest of the polar bear genome - that isolates the result precisely to the presence or absence of the gene(s) that were inserted or knocked out.

If a polar bear gene is inserted into a mouse, that gene gets to interact with the rest of the mouse DNA, which is quite different from the polar bear DNA and quite likely to produce different results. Such an experiment would attempt to vary two factors at the same time, thus making the results very difficult to interpret. That's a very different (and much worse) situation than the experiment in which only one factor is varied (the gene insertion(s) / deletion(s)), where the cause of the experimental results will be much, much easier to clearly and credibly identify.

Edit: or gene replacementThese are newly evolved genes specific to polar bears, which is clearly explained in the article. Ther are no related genes in smaller model organisms. Dropping polar bear genes into mice runs a very high risk of distorted results. These genes need to be studied in polar bears, not in foreign organisms.

They're not new genes specific to polar bears. Rather, they're changes to existing genes shared with a variety of organisms. It would probably be easier to make transgenic mice strains with the same modified genes and get some sense of them that way.This depends right? It depends on if these genese are in the common sections of proteins or in some part that's bear specific.They're bear specific, which is clearly explained in the article...

when they looked for genes that have changed rapidly, they came up with so many other things. One of the most obvious is a gene involved in cholesterol metabolism. Despite all the time since their split from a common ancestor, panda bears and brown bears have no differences in this gene. In contrast, polar bears have picked up nine different changes in this gene in the 400,000 years or so that they've been breeding separately.

A quick look into UniGene shows that the APOB gene is very widespread. Including mice and humans. In fact, looking at the actual publication, the gene in Table 1 are all known in other organisms.

So messing with APOB in mice is almost certainly the next step. Knock in a version that has the polar bear changes and see how resistant the mice are to cholesterol.

While I don't have a solution to animal testing, the casual suggestions of just creating knock-outs so we could understand something and/or potentially exploit the genes of interest for medical purposes make me cringe...

Sorry, animal rights isn't the theme of this thread but I couldn't help it.

Edit: or gene replacementThese are newly evolved genes specific to polar bears, which is clearly explained in the article. Ther are no related genes in smaller model organisms. Dropping polar bear genes into mice runs a very high risk of distorted results. These genes need to be studied in polar bears, not in foreign organisms.

They're not new genes specific to polar bears. Rather, they're changes to existing genes shared with a variety of organisms. It would probably be easier to make transgenic mice strains with the same modified genes and get some sense of them that way.This depends right? It depends on if these genese are in the common sections of proteins or in some part that's bear specific.They're bear specific, which is clearly explained in the article...

when they looked for genes that have changed rapidly, they came up with so many other things. One of the most obvious is a gene involved in cholesterol metabolism. Despite all the time since their split from a common ancestor, panda bears and brown bears have no differences in this gene. In contrast, polar bears have picked up nine different changes in this gene in the 400,000 years or so that they've been breeding separately.

A quick look into UniGene shows that the APOB gene is very widespread. Including mice and humans. In fact, looking at the actual publication, the gene in Table 1 are all known in other organisms.

So messing with APOB in mice is almost certainly the next step. Knock in a version that has the polar bear changes and see how resistant the mice are to cholesterol.

Many drugs that have results in mice that would be very desirable to have in humans don't actually have the same effects in humans and therefore fail to be marketable. When you move to a different organism, the results are quite likely to be different. Yes, try it with the mice and see what happens, but don't be surprised if the results of polar bear testing are radically different from the results of mouse testing. It's the polar bear knockout testing, using the SAME polar bear genomic context, that will give the clearest and most accurate understanding of the exact effects of these new polar bear genes.

It's amazing how fast mammals can evolve when under extreme selection pressure.

Take the case of trying to breed less aggressive wolves in Russia for fur coats. By breeding the most captive wolves with one another in just a couple of generations you've got something that's very much like a dog. In fact, the entire experiment was abandoned because in addition to breeding less aggressive wolves the subsequent generations had a different color and type of fur - again more akin to a dog.

"Researchers involved with the Framingham Heart Study found that in men and women 50 and older, “total cholesterol per se is not a risk factor for coronary heart disease at all.”

Indeed, what the Framingham researchers meant in 1977 when they described LDL cholesterol as a “marginal risk factor” is that a large proportion of people who suffer heart attacks have relatively low LDL cholesterol."

Yeah, people really need to quit thinking ALL cholesterol is BAD cholesterol. I highly doubt polar bears are eating shortening and margarine coupled with highly processed flours and sugars, which is what raises BAD cholesterol. Instead, they are eating fat-rich meats which contain GOOD cholesterol.

Heart disease is often the result of bad cholesterol out-pacing the good.

Polar bears have taken up a blubber-rich diet that may leave them with up to half their body weight made up by fat. And as it turns out, most of the polar bear's genes that have undergone rapid evolution seem to be involved in keeping its cholesterol under control and its heart from exploding under the strain.

I imagine our so called "obesity" problem, is us actually evolving to survive on such a diet.

Many drugs that have results in mice that would be very desirable to have in humans don't actually have the same effects in humans and therefore fail to be marketable. When you move to a different organism, the results are quite likely to be different. Yes, try it with the mice and see what happens, but don't be surprised if the results of polar bear testing are radically different from the results of mouse testing. It's the polar bear knockout testing, using the SAME polar bear genomic context, that will give the clearest and most accurate understanding of the exact effects of these new polar bear genes.

Disclosure: I'm a molecular biologist with significant experience in the pharma industry.

The fact that mice and humans react differently to drugs is a well-known phenomena and there are actually tests that can predict human reaction based on mouse reactions. In addition, just because a specific drug doesn't function the same way doesn't mean the structure of the drug can't be modified ot better perform in humans.

However, talk of drugs at this point is really premature. Right now all the paper has is a bunch of mutations to known genes that seem to allow polar bear hearts to function in high-cholesterol environments. They don't really delve into which mutations are useful for that and which aren't. Sorting that out will require a lot of work.

Finally, nobody, and I mean nobody, is funding a drug study in polar bears. They have way too long a generation time, nobody has worked out how to do gene manipulation with polar bears and lastly every single funding agency is going to die laughing at anyone who proposes this.

The 20,000 generation number isn't nearly as important as 'extreme pressure to adapt' which seems to be a euphemism for 'Bears not exhibiting desirable physical characteristics suffered extreme mortality rates'.

Which leads me to wonder: Do the Inuit (Eskimos) also exhibit similar adaptations to survive their diet? Their traditional sources of food are almost the exact same as polar bears.

Polar bears have taken up a blubber-rich diet that may leave them with up to half their body weight made up by fat. And as it turns out, most of the polar bear's genes that have undergone rapid evolution seem to be involved in keeping its cholesterol under control and its heart from exploding under the strain.

I imagine our so called "obesity" problem, is us actually evolving to survive on such a diet.

Obese people have higher mortality rates, so at best, the obesity problem is the sign of changing selection pressure, due to changing diets. Since that has only been happening on a large scale (ahem) for a couple generations, there probably hasn't been any noticeable adaptation/evolution. But if it continues for another thousand years or so, then we would see some population-wide changes to cardiovascular system genes, like the polar bears.

Yes, some knockouts or combinations of knockouts cause embryonic lethality or other problems. That's a result worth noting. Other knockouts or combinations of knockouts will have other effects, also results worth noting. Getting all of these results is the goal of doing the research in the first place.

Genes often aren't context-free. They often interact with other genes located far away. When a polar bear gene interacts with the rest of the polar bear genome - or, via the knockout process, fails to interact with the rest of the polar bear genome - that isolates the result precisely to the presence or absence of the gene(s) that were inserted or knocked out.

If a polar bear gene is inserted into a mouse, that gene gets to interact with the rest of the mouse DNA, which is quite different from the polar bear DNA and quite likely to produce different results. Such an experiment would attempt to vary two factors at the same time, thus making the results very difficult to interpret. That's a very different (and much worse) situation than the experiment in which only one factor is varied (the gene insertion(s) / deletion(s)), where the cause of the experimental results will be much, much easier to clearly and credibly identify.

Here's the problem, though: you complain that results in mice aren't necessarily applicable to humans, but imply that results in polar bears are somehow going to be. We don't care what the genes do in polar bears. And for that matter, at this point we don't care what they do in interaction with one another. The very first thing we need to do is characterize the effects of each individual modification before we worry about bigger picture stuff.

And polar bear DNA is no different from mouse DNA. DNA is DNA. Laboratory mice have the added benefit of being so inbred that they are very nearly genetically identical to one another. By replacing a normal gene in a mouse with the modified polar bear version of that same gene, we can see exactly the results of that gene and that gene alone without worrying about everything else that's going on. By doing these experiments in mice we get more control than we would ever get in polar bears; there's far less genetic diversity in the background genome. By doing this in polar bears directly, you don't know how different the background genome is between any two organisms and so can't really judge what is responsible for any effects you might see. That would make the results much more difficult to interpret.

If you ask what separates two species, a lot of people would tell you that an inability to produce fertile offspring is the key test....Despite a number of very obvious features that distinguish the polar bear from other bears, it readily produces fertile offspring with brown bears.

Then does biology still consider polar bears and brown bears to be separate species? Because the evidence shows that such a classification is inaccurate.

Quote:

And as it turns out, most of the polar bear's genes that have undergone rapid evolution seem to be involved in keeping its cholesterol under control and its heart from exploding under the strain.

Does biology recognize 'races' within non-human species? Different human 'races' have different genetic susceptibility to things like cholesterol problems and diabetes. Sounds to me like the polar and brown bears are just different races of the same species.

Compare the proteins expressed in polar bears to the proteins expressed in brown bears. Any drugs created are less likely to be based off of DNA or RNA and will be more likely to be based off of the Proteins generated by that DNA.

How structurally different is a polar bear heart from that of a brown bear. Is is possible, the difference is less related to bio chemistry and more related to bio mechanics?

Honestly, I think it is all related to the polar bears using hydrogen peroxide containing hair coloring agents.

If you ask what separates two species, a lot of people would tell you that an inability to produce fertile offspring is the key test....Despite a number of very obvious features that distinguish the polar bear from other bears, it readily produces fertile offspring with brown bears.

Then does biology still consider polar bears and brown bears to be separate species? Because the evidence shows that such a classification is inaccurate.

Quote:

And as it turns out, most of the polar bear's genes that have undergone rapid evolution seem to be involved in keeping its cholesterol under control and its heart from exploding under the strain.

Does biology recognize 'races' within non-human species? Different human 'races' have different genetic susceptibility to things like cholesterol problems and diabetes. Sounds to me like the polar and brown bears are just different races of the same species.

There aren't really any hard boundaries in biology. The real biological unit is a substantially interacting and genetically-intermixing population. Some populations are more similar to each other or different from each other. Some can reproduce if they got together, some never would even if they were around each other for reasons other than strict fertility (mating rituals, pheromones, etc.)

So in short: yes, there can be "races" of sorts within what we consider to be species. But what we consider to be species is a bit more fluid than just whether two animals getting together can produce a fertile offspring. EDIT: Generally the biological term is "subspecies"

Yeah, people really need to quit thinking ALL cholesterol is BAD cholesterol. I highly doubt polar bears are eating shortening and margarine coupled with highly processed flours and sugars, which is what raises BAD cholesterol. Instead, they are eating fat-rich meats which contain GOOD cholesterol.

Heart disease is often the result of bad cholesterol out-pacing the good.

Cholesterol in a diet, regardless of source is neither "good" nor "bad", it is simply cholesterol. Ignoring the debate as to whether LDL=bad, HDL=good is correct, complete bunkum, or qualifiedly correct, cholesterol absorbed from the GI tract is turned into a form of LDL to be transported from the gut, and the transporting LDL later gets modified in many ways, some of which you would probably not want to have as major components of your circulating cholesterol. Cholesterol can also get transferred from cells or LDL to HDL particles, which if they are efficiently reabsorbed by the liver are probably deserving of the monicker "good cholesterol". As these are bears, it would of course be most appropriate if the main effect of the genetic changes were to give them predominantly "fluffy" LDL, which seems to be the white sheep of the LDL family.